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Dopamine and somatostatin have been implicated in the pathophysiology of depression. We have employed in vivo microdialysis to investigate the regulation of dopamine release by somatostatin in the nucleus accumbens and the striatum of awake, freely moving rats, and to ascertain how this regulation may be affected by desipramine treatment. Somatostatin-14 (10(-4) M) infusion induced an increase in the release of dopamine and a decrease in the release of its metabolites in both the nucleus accumbens (568% of basal) and the striatum (546% of basal). Chronic desipramine treatment resulted in an exaggerated somatostatin-induced increase of dopamine levels, specifically in the nucleus accumbens (3542% compared with 564% of basal in the striatum), whereas acute desipramine treatment had no effect (582% of basal) compared with saline treated rats. Basal concentrations of dopamine and metabolites were not influenced by either chronic or acute treatment of desipramine in either brain area. These results demonstrate that somatostatin regulates dopamine release in the nucleus accumbens and the striatum. Chronic antidepressant treatment influences somatostatin's actions on dopamine function selectively in the nucleus accumbens.

Cognitive deficits are core features of schizophrenia and considered putative endophenotypes. This study assessed the familial pattern of deficits in sustained attention, working memory and executive function in remitted-schizophrenia patients and their unaffected siblings. Sixteen patients, 16 unaffected siblings, and 17 healthy control subjects underwent a battery of neuropsychological tasks that have so far yielded mixed findings in performance differences. Both groups had prolonged reaction times compared with controls in sustained attention tasks; the siblings made more false alarms in the working memory task, but only the patients' performance was poorer in the executive function tasks. These findings further support sustained attention and working memory deficits as potential endophenotypes of schizophrenia. Reaction time and false alarm rates are suggested as additional useful endophenotypic measures that could potentially account for differences in performance in tasks that are not purported to examine the specific measures per se.

This study investigated how the administration (acute and chronic) of the antidepressants citalopram and desmethylimipramine (DMI) influences somatostatin (somatotropin release inhibitory factor, SRIF) levels and SRIF receptor density (sst 1-5 ) in rat brain. Animals received either of the following treatments: (1) saline for 21 days (control group), (2) saline for 20 days and citalopram or DMI for 1 day (citalopram or DMI acute groups), (3) citalopram or DMI for 21 days (citalopram or DMI chronic groups). Somatostatin levels were determined by radioimmunoassay. [ 125 I]LTT SRIF-28 binding in the absence (labeling of sst 1-5 ) or presence of 3 nM MK678 (labeling of sst 1/4 ) and [ 125 I]Tyr 3 octreotide (labeling of sst 2/5 ) binding with subsequent autoradiography was performed in brains of rats treated with both antidepressants. Somatostatin levels were increased after citalopram, but not DMI administration, in the caudate-putamen, hippocampus, nucleus accumbens, and prefrontal cortex. Autoradiography studies illustrated a significant decrease in receptor density in the superficial and deep layers of frontal cortex (sst 2 ), as well as a significant increase in the CA1 (sst 1/4 ) hippocampal field in brains of chronically citalopram-treated animals. DMI administration increased sst 1/4 receptors levels in the CA1 hippocampal region. These results suggest that citalopram and to a lesser extent DMI influence the function of the somatostatin system in brain regions involved in the emotional, motivational, and cognitive aspects of behavior.